SEATTLE – A new study finds that patients with both multiple sclerosis (MS) and restless legs syndrome (RLS) were more likely to suffer from self-perceived cognitive impairment. The results suggest that sleep dysfunction exacerbated by RLS could affect cognition in patients with MS, study lead author Katie L. Cederberg, CPT, a doctoral student in the department of physical therapy at the University of Alabama at Birmingham, said in an interview. She spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

“RLS severity did predict cognitive impairment,” she said. However, she added, “this is just a snapshot, and we need to do more research.”

Sleep problems, including RLS, are more common in patients with MS than in the general population. “Current research suggests that anywhere from 19% to 67% of individuals with MS experience some sort of sleep difficulty, with rates as high as 80% in some samples,” a 2015 report noted.

As for RLS, a 2018 systematic review and meta-analysis found that “pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than among male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (odds ratio, 3.96, 95% confidence interval, 3.29-4.77, P less than .001) (Sleep Med. 2018 Oct;50:97-104).

Ms. Cederberg said the frequency of RLS in patients with MS spurred her and colleagues to explore whether it may affect cognitive function.

For their study, the researchers surveyed 275 patients with MS (mean age = 60, 81% female, 33% employed, 95% white, 66% with relapsing-remitting MS). Of the 275, 75 appeared to have RLS. These patients were similar to the non-RLS patients in multiple areas, but they diverged in scores on the brief Multiple Sclerosis Neuropsychological Questionnaire, which measures self-perception of cognition.

Those with both MS and RLS scored 21.9 (± 11.7) on the test, while those with MS scored 18.0 (± 11.0), P = 0.023.

Analyses linked greater RLS severity to worse self-perceived cognitive impairment and sleep quality. “The diagnosis and treatment of RLS symptoms and other effectors of sleep quality could improve cognitive consequences of MS,” the authors concluded.

The National MS Society funded the study. The study authors reported no relevant disclosures.

SEATTLE – A new study finds that patients with both multiple sclerosis (MS) and restless legs syndrome (RLS) were more likely to suffer from self-perceived cognitive impairment. The results suggest that sleep dysfunction exacerbated by RLS could affect cognition in patients with MS, study lead author Katie L. Cederberg, CPT, a doctoral student in the department of physical therapy at the University of Alabama at Birmingham, said in an interview. She spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

“RLS severity did predict cognitive impairment,” she said. However, she added, “this is just a snapshot, and we need to do more research.”

Sleep problems, including RLS, are more common in patients with MS than in the general population. “Current research suggests that anywhere from 19% to 67% of individuals with MS experience some sort of sleep difficulty, with rates as high as 80% in some samples,” a 2015 report noted.

As for RLS, a 2018 systematic review and meta-analysis found that “pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than among male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (odds ratio, 3.96, 95% confidence interval, 3.29-4.77, P less than .001) (Sleep Med. 2018 Oct;50:97-104).

Ms. Cederberg said the frequency of RLS in patients with MS spurred her and colleagues to explore whether it may affect cognitive function.

For their study, the researchers surveyed 275 patients with MS (mean age = 60, 81% female, 33% employed, 95% white, 66% with relapsing-remitting MS). Of the 275, 75 appeared to have RLS. These patients were similar to the non-RLS patients in multiple areas, but they diverged in scores on the brief Multiple Sclerosis Neuropsychological Questionnaire, which measures self-perception of cognition.

Those with both MS and RLS scored 21.9 (± 11.7) on the test, while those with MS scored 18.0 (± 11.0), P = 0.023.

Analyses linked greater RLS severity to worse self-perceived cognitive impairment and sleep quality. “The diagnosis and treatment of RLS symptoms and other effectors of sleep quality could improve cognitive consequences of MS,” the authors concluded.

The National MS Society funded the study. The study authors reported no relevant disclosures.

SEATTLE – A new study finds that patients with both multiple sclerosis (MS) and restless legs syndrome (RLS) were more likely to suffer from self-perceived cognitive impairment. The results suggest that sleep dysfunction exacerbated by RLS could affect cognition in patients with MS, study lead author Katie L. Cederberg, CPT, a doctoral student in the department of physical therapy at the University of Alabama at Birmingham, said in an interview. She spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

“RLS severity did predict cognitive impairment,” she said. However, she added, “this is just a snapshot, and we need to do more research.”

Sleep problems, including RLS, are more common in patients with MS than in the general population. “Current research suggests that anywhere from 19% to 67% of individuals with MS experience some sort of sleep difficulty, with rates as high as 80% in some samples,” a 2015 report noted.

As for RLS, a 2018 systematic review and meta-analysis found that “pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than among male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (odds ratio, 3.96, 95% confidence interval, 3.29-4.77, P less than .001) (Sleep Med. 2018 Oct;50:97-104).

Ms. Cederberg said the frequency of RLS in patients with MS spurred her and colleagues to explore whether it may affect cognitive function.

For their study, the researchers surveyed 275 patients with MS (mean age = 60, 81% female, 33% employed, 95% white, 66% with relapsing-remitting MS). Of the 275, 75 appeared to have RLS. These patients were similar to the non-RLS patients in multiple areas, but they diverged in scores on the brief Multiple Sclerosis Neuropsychological Questionnaire, which measures self-perception of cognition.

Those with both MS and RLS scored 21.9 (± 11.7) on the test, while those with MS scored 18.0 (± 11.0), P = 0.023.

Analyses linked greater RLS severity to worse self-perceived cognitive impairment and sleep quality. “The diagnosis and treatment of RLS symptoms and other effectors of sleep quality could improve cognitive consequences of MS,” the authors concluded.

The National MS Society funded the study. The study authors reported no relevant disclosures.

SEATTLE – Researchers are working on new tools to objectively measure several domains affected by multiple sclerosis (MS) in hope of improving patient care, according to Jared Srinivasan.

Mr. Srinivasan, a research coordinator at South Shore Neurologic Associates in Patchogue, N.Y., sat down at the annual meeting of the Consortium of Multiple Sclerosis Centers for a video interview summarizing his work on new measurement tools for assessing disease status in MS patients with Mark Gudesblatt, MD, and other colleagues at South Shore Neurologic Associates.

“We are trying to find better ways of measuring disease status, rather than the EDSS [Expanded Disability Status Scale] ... It is not as sensitive as some other measures can be,” Mr. Srinivasan said. “We are trying to shed light on some new tools regarding objectively measuring cognition, manual dexterity, gait, and ocular coherence tomography.”

The overall goal, he said, “is to use a combination of these granular outcome measures to create a bigger picture of a patient’s disease so we can better treat them.”

One of the tools is called Neurotrax, which measures cognition in multiple dimensions (e.g., attention, information processing, motor skills, verbal functioning). With this and other new tools for manual dexterity and its cognitive aspects, as well as other dimensions of MS, the researchers are trying capture a fuller picture of MS in individual patients.

“The end goal of this is that if we can show that MS is such a complex disease that the current tools we are using do not quite capture the full nuances and granularity in it, then we can move toward using better measures that will capture that, which will move patient care forward.”

Mr. Srinivasan had nothing to disclose.

[email protected]

SEATTLE – Researchers are working on new tools to objectively measure several domains affected by multiple sclerosis (MS) in hope of improving patient care, according to Jared Srinivasan.

Mr. Srinivasan, a research coordinator at South Shore Neurologic Associates in Patchogue, N.Y., sat down at the annual meeting of the Consortium of Multiple Sclerosis Centers for a video interview summarizing his work on new measurement tools for assessing disease status in MS patients with Mark Gudesblatt, MD, and other colleagues at South Shore Neurologic Associates.

“We are trying to find better ways of measuring disease status, rather than the EDSS [Expanded Disability Status Scale] ... It is not as sensitive as some other measures can be,” Mr. Srinivasan said. “We are trying to shed light on some new tools regarding objectively measuring cognition, manual dexterity, gait, and ocular coherence tomography.”

The overall goal, he said, “is to use a combination of these granular outcome measures to create a bigger picture of a patient’s disease so we can better treat them.”

One of the tools is called Neurotrax, which measures cognition in multiple dimensions (e.g., attention, information processing, motor skills, verbal functioning). With this and other new tools for manual dexterity and its cognitive aspects, as well as other dimensions of MS, the researchers are trying capture a fuller picture of MS in individual patients.

“The end goal of this is that if we can show that MS is such a complex disease that the current tools we are using do not quite capture the full nuances and granularity in it, then we can move toward using better measures that will capture that, which will move patient care forward.”

Mr. Srinivasan had nothing to disclose.

[email protected]

SEATTLE – Researchers are working on new tools to objectively measure several domains affected by multiple sclerosis (MS) in hope of improving patient care, according to Jared Srinivasan.

Mr. Srinivasan, a research coordinator at South Shore Neurologic Associates in Patchogue, N.Y., sat down at the annual meeting of the Consortium of Multiple Sclerosis Centers for a video interview summarizing his work on new measurement tools for assessing disease status in MS patients with Mark Gudesblatt, MD, and other colleagues at South Shore Neurologic Associates.

“We are trying to find better ways of measuring disease status, rather than the EDSS [Expanded Disability Status Scale] ... It is not as sensitive as some other measures can be,” Mr. Srinivasan said. “We are trying to shed light on some new tools regarding objectively measuring cognition, manual dexterity, gait, and ocular coherence tomography.”

The overall goal, he said, “is to use a combination of these granular outcome measures to create a bigger picture of a patient’s disease so we can better treat them.”

One of the tools is called Neurotrax, which measures cognition in multiple dimensions (e.g., attention, information processing, motor skills, verbal functioning). With this and other new tools for manual dexterity and its cognitive aspects, as well as other dimensions of MS, the researchers are trying capture a fuller picture of MS in individual patients.

“The end goal of this is that if we can show that MS is such a complex disease that the current tools we are using do not quite capture the full nuances and granularity in it, then we can move toward using better measures that will capture that, which will move patient care forward.”

Mr. Srinivasan had nothing to disclose.

[email protected]

SEATTLE – Patients with multiple sclerosis (MS) may be able to improve cognitive function through a brief course in mindfulness meditation, a new report suggests.

“The present study demonstrated significant improvement in processing speed, a core area of impairment in individuals with MS, following 4 weeks of mindfulness meditation,” said lead author Heena R. Manglani, a graduate student at the Ohio State University, Columbus. She spoke in an interview and in a presentation about the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

An estimated 43%-70% of people with MS experience cognitive decline. This decline “has a sophisticated neuroanatomic and pathophysiologic background and disturbs such vital cognitive domains as speed of information processing, memory, attention, executive functions, and visual perceptual function,” reported the authors of a 2017 review (Rev Neurosci. 2017 Nov 27;28[8]:845-860).

For the new study, researchers tested two strategies for cognitive enhancement in patients with MS. All study participants were aged 31-59 years and relapse free within the previous 30 days; most had relapsing remitting MS, and most did not show signs of cognitive decline.

The researchers assigned 20 patients to a 4-week adaptive computerized cognitive training program and 20 patients to a 4-week mindfulness meditation training program. Another 21 patients were assigned to a control group.

The adaptive training program relied on computerized games designed to boost processing speed, attention, and working memory. The mindfulness training focused on components such as awareness of breathing and of bodily sensations.

Researchers found that “the magnitude of cognitive gain from pre- to post training was greatest in participants in the mindfulness group, who did better than participants in either of the other two groups,” Ms. Manglani said.

Compared with the adaptive cognitive training and the control group, she said, the mindfulness meditation group showed statistically significant improvement in processing speed per scores on the Symbol Digit Modalities Test, which rose from 52.2 before training to 58.4 post training.

The interventions did not appear to have any effect on Paced Auditory Serial Addition scores, which measure working memory.

The findings suggest that “less than 20 hours of mindfulness may be effective in significantly improving processing speed in MS,” Ms. Manglani said. “It is much shorter than a typically delivered program. We hypothesize that you are training attention with mindfulness training. Attention has a lot of overlap with processing speed.”

Ms. Manglani noted that this was a pilot study, and she acknowledged that fairly few participants – only five or six in each group – showed signs of cognitive decline. The study also did not explore whether cognitive improvements translated to real-life changes in cognition.

“This effect needs to be replicated in a larger sample,” Ms. Manglani said, “and future studies are needed to establish the lasting effects of such training and how improvements in cognitive function may generalize to greater engagement in vocational and leisure activities and higher quality of life.”

The study was funded by the National Multiple Sclerosis Society and the National Institutes of Health. The authors reported no relevant disclosures except for one coauthor who received honoraria from Sanofi Genzyme and funding from the National Multiple Sclerosis Society and the NIH.
 

SEATTLE – Patients with multiple sclerosis (MS) may be able to improve cognitive function through a brief course in mindfulness meditation, a new report suggests.

“The present study demonstrated significant improvement in processing speed, a core area of impairment in individuals with MS, following 4 weeks of mindfulness meditation,” said lead author Heena R. Manglani, a graduate student at the Ohio State University, Columbus. She spoke in an interview and in a presentation about the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

An estimated 43%-70% of people with MS experience cognitive decline. This decline “has a sophisticated neuroanatomic and pathophysiologic background and disturbs such vital cognitive domains as speed of information processing, memory, attention, executive functions, and visual perceptual function,” reported the authors of a 2017 review (Rev Neurosci. 2017 Nov 27;28[8]:845-860).

For the new study, researchers tested two strategies for cognitive enhancement in patients with MS. All study participants were aged 31-59 years and relapse free within the previous 30 days; most had relapsing remitting MS, and most did not show signs of cognitive decline.

The researchers assigned 20 patients to a 4-week adaptive computerized cognitive training program and 20 patients to a 4-week mindfulness meditation training program. Another 21 patients were assigned to a control group.

The adaptive training program relied on computerized games designed to boost processing speed, attention, and working memory. The mindfulness training focused on components such as awareness of breathing and of bodily sensations.

Researchers found that “the magnitude of cognitive gain from pre- to post training was greatest in participants in the mindfulness group, who did better than participants in either of the other two groups,” Ms. Manglani said.

Compared with the adaptive cognitive training and the control group, she said, the mindfulness meditation group showed statistically significant improvement in processing speed per scores on the Symbol Digit Modalities Test, which rose from 52.2 before training to 58.4 post training.

The interventions did not appear to have any effect on Paced Auditory Serial Addition scores, which measure working memory.

The findings suggest that “less than 20 hours of mindfulness may be effective in significantly improving processing speed in MS,” Ms. Manglani said. “It is much shorter than a typically delivered program. We hypothesize that you are training attention with mindfulness training. Attention has a lot of overlap with processing speed.”

Ms. Manglani noted that this was a pilot study, and she acknowledged that fairly few participants – only five or six in each group – showed signs of cognitive decline. The study also did not explore whether cognitive improvements translated to real-life changes in cognition.

“This effect needs to be replicated in a larger sample,” Ms. Manglani said, “and future studies are needed to establish the lasting effects of such training and how improvements in cognitive function may generalize to greater engagement in vocational and leisure activities and higher quality of life.”

The study was funded by the National Multiple Sclerosis Society and the National Institutes of Health. The authors reported no relevant disclosures except for one coauthor who received honoraria from Sanofi Genzyme and funding from the National Multiple Sclerosis Society and the NIH.
 

SEATTLE – Patients with multiple sclerosis (MS) may be able to improve cognitive function through a brief course in mindfulness meditation, a new report suggests.

“The present study demonstrated significant improvement in processing speed, a core area of impairment in individuals with MS, following 4 weeks of mindfulness meditation,” said lead author Heena R. Manglani, a graduate student at the Ohio State University, Columbus. She spoke in an interview and in a presentation about the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

An estimated 43%-70% of people with MS experience cognitive decline. This decline “has a sophisticated neuroanatomic and pathophysiologic background and disturbs such vital cognitive domains as speed of information processing, memory, attention, executive functions, and visual perceptual function,” reported the authors of a 2017 review (Rev Neurosci. 2017 Nov 27;28[8]:845-860).

For the new study, researchers tested two strategies for cognitive enhancement in patients with MS. All study participants were aged 31-59 years and relapse free within the previous 30 days; most had relapsing remitting MS, and most did not show signs of cognitive decline.

The researchers assigned 20 patients to a 4-week adaptive computerized cognitive training program and 20 patients to a 4-week mindfulness meditation training program. Another 21 patients were assigned to a control group.

The adaptive training program relied on computerized games designed to boost processing speed, attention, and working memory. The mindfulness training focused on components such as awareness of breathing and of bodily sensations.

Researchers found that “the magnitude of cognitive gain from pre- to post training was greatest in participants in the mindfulness group, who did better than participants in either of the other two groups,” Ms. Manglani said.

Compared with the adaptive cognitive training and the control group, she said, the mindfulness meditation group showed statistically significant improvement in processing speed per scores on the Symbol Digit Modalities Test, which rose from 52.2 before training to 58.4 post training.

The interventions did not appear to have any effect on Paced Auditory Serial Addition scores, which measure working memory.

The findings suggest that “less than 20 hours of mindfulness may be effective in significantly improving processing speed in MS,” Ms. Manglani said. “It is much shorter than a typically delivered program. We hypothesize that you are training attention with mindfulness training. Attention has a lot of overlap with processing speed.”

Ms. Manglani noted that this was a pilot study, and she acknowledged that fairly few participants – only five or six in each group – showed signs of cognitive decline. The study also did not explore whether cognitive improvements translated to real-life changes in cognition.

“This effect needs to be replicated in a larger sample,” Ms. Manglani said, “and future studies are needed to establish the lasting effects of such training and how improvements in cognitive function may generalize to greater engagement in vocational and leisure activities and higher quality of life.”

The study was funded by the National Multiple Sclerosis Society and the National Institutes of Health. The authors reported no relevant disclosures except for one coauthor who received honoraria from Sanofi Genzyme and funding from the National Multiple Sclerosis Society and the NIH.
 

When you have a few spare minutes on your lunch break, walk by the grade school playground in your neighborhood. Even at a quick glance you will notice that almost all the children are in motion – running, chasing, or being chased. Don’t linger too long or make repeat visits because unfortunately your presence may raise suspicions about your motives. But, even on your brief visit, you will also notice that there are a few children who are sitting down either chatting with a classmate or playing by themselves. If despite my caution you returned several days in a row, you would have noticed that the sedentary outliers tend to be the same children.

©Jupiterimages/Thinkstock.com

Some of the children playing alone simply may be shy loners or socially inept. But I’ve always suspected that there are some people who come in the world genetically predisposed to being sedentary. You can try to make the environment more enticing and stimulating, but the children predestined to be inactive will choose to sit and watch. Not surprisingly, most of those less active children are predestined to be overweight and obese.

At least as young children we seem to be driven to be active, and it is the few outliers who are sedentary. A recent investigation from the department of health and kinesiology at Texas A&M University at College Station is beginning to shed some light on when in our evolutionary history the urge to be active was incorporated into our genome (PLOS ONE. 2019 Apr 29. doi: 10.1371/journal.pone.0216155). The researchers found that snippets of DNA already known to be associated with levels of activity emerged in our ancestors before we were Homo sapiens about 500,000 years ago. This finding surprised the investigators who had suspected that this incorporation of a gene sequence driving activity was more likely to have occurred ten thousand years ago when subsistence farming and its physical demands first appeared.

The authors now postulate that the drive to be active coincided as pre–Homo sapiens grew larger and moved from a treed landscape into the open savanna (“To Move Is to Thrive. It’s in Our Genes” by Gretchen Reynolds. The New York Times, May 15, 2019). As J. Timothy Lightfoot, the senior investigator, observed, “If you were lazy then, you did not survive.”

So if the drive to be active is so deeply buried in our genome why have we slipped so easily into a species in which being sedentary is the norm? Our observation of a playground in contact motion is probably evidence that those snippets of DNA still are buried in our genome. However, it is abundantly clear that in North America one doesn’t need to be active to survive, at least in the sense of being reproductively fit. It only takes a few us who must be physically active to grow and build things that we in the sedentary majority can buy or trade for.

There are some of us who have inherited some DNA snippets that drive us to be active post early childhood. My father walked two or three times a day until a few months before his death at 92, and not because someone told him it do it for his health. Like him, I just feel better if I have spent a couple of hours being active every day.

The challenge for us as pediatricians is to help families create environments that foster continued activity by discouraging sedentary entertainments and modeling active lifestyles. For example, simple things like choosing a spot at the periphery of the parking lot instead of close to the store. Choosing stairs instead of the elevator. Of course, anything you will be doing is artificial because the truth is we don’t need to be active to survive even though the urge to move is deeply rooted in our genes.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

When you have a few spare minutes on your lunch break, walk by the grade school playground in your neighborhood. Even at a quick glance you will notice that almost all the children are in motion – running, chasing, or being chased. Don’t linger too long or make repeat visits because unfortunately your presence may raise suspicions about your motives. But, even on your brief visit, you will also notice that there are a few children who are sitting down either chatting with a classmate or playing by themselves. If despite my caution you returned several days in a row, you would have noticed that the sedentary outliers tend to be the same children.

©Jupiterimages/Thinkstock.com

Some of the children playing alone simply may be shy loners or socially inept. But I’ve always suspected that there are some people who come in the world genetically predisposed to being sedentary. You can try to make the environment more enticing and stimulating, but the children predestined to be inactive will choose to sit and watch. Not surprisingly, most of those less active children are predestined to be overweight and obese.

At least as young children we seem to be driven to be active, and it is the few outliers who are sedentary. A recent investigation from the department of health and kinesiology at Texas A&M University at College Station is beginning to shed some light on when in our evolutionary history the urge to be active was incorporated into our genome (PLOS ONE. 2019 Apr 29. doi: 10.1371/journal.pone.0216155). The researchers found that snippets of DNA already known to be associated with levels of activity emerged in our ancestors before we were Homo sapiens about 500,000 years ago. This finding surprised the investigators who had suspected that this incorporation of a gene sequence driving activity was more likely to have occurred ten thousand years ago when subsistence farming and its physical demands first appeared.

The authors now postulate that the drive to be active coincided as pre–Homo sapiens grew larger and moved from a treed landscape into the open savanna (“To Move Is to Thrive. It’s in Our Genes” by Gretchen Reynolds. The New York Times, May 15, 2019). As J. Timothy Lightfoot, the senior investigator, observed, “If you were lazy then, you did not survive.”

So if the drive to be active is so deeply buried in our genome why have we slipped so easily into a species in which being sedentary is the norm? Our observation of a playground in contact motion is probably evidence that those snippets of DNA still are buried in our genome. However, it is abundantly clear that in North America one doesn’t need to be active to survive, at least in the sense of being reproductively fit. It only takes a few us who must be physically active to grow and build things that we in the sedentary majority can buy or trade for.

There are some of us who have inherited some DNA snippets that drive us to be active post early childhood. My father walked two or three times a day until a few months before his death at 92, and not because someone told him it do it for his health. Like him, I just feel better if I have spent a couple of hours being active every day.

The challenge for us as pediatricians is to help families create environments that foster continued activity by discouraging sedentary entertainments and modeling active lifestyles. For example, simple things like choosing a spot at the periphery of the parking lot instead of close to the store. Choosing stairs instead of the elevator. Of course, anything you will be doing is artificial because the truth is we don’t need to be active to survive even though the urge to move is deeply rooted in our genes.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

When you have a few spare minutes on your lunch break, walk by the grade school playground in your neighborhood. Even at a quick glance you will notice that almost all the children are in motion – running, chasing, or being chased. Don’t linger too long or make repeat visits because unfortunately your presence may raise suspicions about your motives. But, even on your brief visit, you will also notice that there are a few children who are sitting down either chatting with a classmate or playing by themselves. If despite my caution you returned several days in a row, you would have noticed that the sedentary outliers tend to be the same children.

©Jupiterimages/Thinkstock.com

Some of the children playing alone simply may be shy loners or socially inept. But I’ve always suspected that there are some people who come in the world genetically predisposed to being sedentary. You can try to make the environment more enticing and stimulating, but the children predestined to be inactive will choose to sit and watch. Not surprisingly, most of those less active children are predestined to be overweight and obese.

At least as young children we seem to be driven to be active, and it is the few outliers who are sedentary. A recent investigation from the department of health and kinesiology at Texas A&M University at College Station is beginning to shed some light on when in our evolutionary history the urge to be active was incorporated into our genome (PLOS ONE. 2019 Apr 29. doi: 10.1371/journal.pone.0216155). The researchers found that snippets of DNA already known to be associated with levels of activity emerged in our ancestors before we were Homo sapiens about 500,000 years ago. This finding surprised the investigators who had suspected that this incorporation of a gene sequence driving activity was more likely to have occurred ten thousand years ago when subsistence farming and its physical demands first appeared.

The authors now postulate that the drive to be active coincided as pre–Homo sapiens grew larger and moved from a treed landscape into the open savanna (“To Move Is to Thrive. It’s in Our Genes” by Gretchen Reynolds. The New York Times, May 15, 2019). As J. Timothy Lightfoot, the senior investigator, observed, “If you were lazy then, you did not survive.”

So if the drive to be active is so deeply buried in our genome why have we slipped so easily into a species in which being sedentary is the norm? Our observation of a playground in contact motion is probably evidence that those snippets of DNA still are buried in our genome. However, it is abundantly clear that in North America one doesn’t need to be active to survive, at least in the sense of being reproductively fit. It only takes a few us who must be physically active to grow and build things that we in the sedentary majority can buy or trade for.

There are some of us who have inherited some DNA snippets that drive us to be active post early childhood. My father walked two or three times a day until a few months before his death at 92, and not because someone told him it do it for his health. Like him, I just feel better if I have spent a couple of hours being active every day.

The challenge for us as pediatricians is to help families create environments that foster continued activity by discouraging sedentary entertainments and modeling active lifestyles. For example, simple things like choosing a spot at the periphery of the parking lot instead of close to the store. Choosing stairs instead of the elevator. Of course, anything you will be doing is artificial because the truth is we don’t need to be active to survive even though the urge to move is deeply rooted in our genes.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

BALTIMORE – Pediatricians appear less comfortable discussing e-cigarettes and their harms with adolescents and parents than they do discussing dangers of tobacco products, according to a recent study.

LiudmylaSupynska/Thinkstock

“Providers are aware of the increased prevalence, harms [of e-cigs] and [the] positive impact of counseling teens about e-cigs,” said Allison Heinly, MD, of Hasbro Children’s Hospital in Providence, R.I., and her colleagues. But, “providers are less likely to ask, advise, or assist parents [and teens] regarding e-cig use, compared to tobacco, and are less comfortable doing so.” The researchers presented their findings at the Pediatric Academic Societies annual meeting.

A variety of concerns exist regarding ingredients in e-cigarettes, Dr. Heinly noted, including nicotine, volatile organic compounds, carcinogenic chemicals, flavorings, and ultra-fine particles.

Dr. Heinly and her associates aimed to assess pediatricians’ knowledge, attitudes, and behaviors toward both teens’ and parents’ use of e-cigarettes, as well as the barrier pediatricians perceived when it came to screening and counseling those who use e-cigarettes.

Among 69 providers at a large Northeastern urban academic primary care clinic who received surveys, 62 responded, primarily residents (84%). The respondents included 44 pediatric residents, eight triple-board residents, and 10 attending physicians.

The researchers collapsed “most of the time”/“always” and “some of the time”/“never” responses into two categories.

Most of the respondents (82%) knew e-cigarettes are the most common tobacco product that youth use, and nearly all (97%) believed e-cigarettes were addictive and harmful to users’ health. In addition, most (79%) believed using e-cigarettes could be a pathway toward students beginning to use other drugs.

Even though respondents believed counseling teens about use of tobacco or e-cigarettes can reduce the likelihood that they will start using them, providers were much less likely to discuss e-cigarettes than tobacco with teens.

Nearly all the doctors (97%) reported asking teens about their use of tobacco, but only about half (52%) asked about e-cigarette use (P less than .001). And only about one in five doctors (21%) reported counseling teens about using e-cigarettes, compared with 47% of those who advised teens regarding tobacco use (P = .002).

Over a third of responding physicians (37%) reported helping adolescent patients quit using tobacco, but just 7% reported doing so with e-cigarettes (P less than .001).

Doctors overwhelmingly reported feeling comfortable talking about tobacco with teens (98%), but fewer felt comfortable discussing e-cigarettes (77%; P less than .001). Respondents similarly were less comfortable discussing e-cigarettes (55%) than tobacco (87%) with parents (P less than .001).

Very few pediatricians asked parents about their use of e-cigarettes (5%) or advised them about e-cigarettes’ harms (7%), and even fewer reported helping parents quit using them (2%). By contrast, more than half of pediatricians (60%) asked parents about smoking or advised them about tobacco use harms (52%), and nearly one-third (31%) reported helping parents quit smoking (P less than .001 for all comparisons).

The biggest barrier to discussing e-cigarettes with families was, as with discussing tobacco, not having enough time. But about twice as many respondents cited insufficient knowledge as a barrier for e-cigarettes as for tobacco (P = .003). A small percentage of respondents (less than 20%) also reported feeling unsure about the harm of e-cigarettes (P = .001).

Lack of training was a significant barrier to physicians’ discussion of e-cigarettes as well. Many more physicians reported receiving training in medical school on tobacco and traditional cigarettes (78%) than on e-cigarettes (13%), possibly because of how recently e-cigarettes have become widely available (P less than .001).

More physicians reported receiving training related to e-cigarettes during residency (36%), but it still fell well short of how many reported other tobacco and smoking training during residency (61%; P = .001).

The findings “emphasize the importance of increasing training about e-cig counseling,” Dr. Heinly and her associates concluded.

The researchers noted no external funding or disclosures.

BALTIMORE – Pediatricians appear less comfortable discussing e-cigarettes and their harms with adolescents and parents than they do discussing dangers of tobacco products, according to a recent study.

LiudmylaSupynska/Thinkstock

“Providers are aware of the increased prevalence, harms [of e-cigs] and [the] positive impact of counseling teens about e-cigs,” said Allison Heinly, MD, of Hasbro Children’s Hospital in Providence, R.I., and her colleagues. But, “providers are less likely to ask, advise, or assist parents [and teens] regarding e-cig use, compared to tobacco, and are less comfortable doing so.” The researchers presented their findings at the Pediatric Academic Societies annual meeting.

A variety of concerns exist regarding ingredients in e-cigarettes, Dr. Heinly noted, including nicotine, volatile organic compounds, carcinogenic chemicals, flavorings, and ultra-fine particles.

Dr. Heinly and her associates aimed to assess pediatricians’ knowledge, attitudes, and behaviors toward both teens’ and parents’ use of e-cigarettes, as well as the barrier pediatricians perceived when it came to screening and counseling those who use e-cigarettes.

Among 69 providers at a large Northeastern urban academic primary care clinic who received surveys, 62 responded, primarily residents (84%). The respondents included 44 pediatric residents, eight triple-board residents, and 10 attending physicians.

The researchers collapsed “most of the time”/“always” and “some of the time”/“never” responses into two categories.

Most of the respondents (82%) knew e-cigarettes are the most common tobacco product that youth use, and nearly all (97%) believed e-cigarettes were addictive and harmful to users’ health. In addition, most (79%) believed using e-cigarettes could be a pathway toward students beginning to use other drugs.

Even though respondents believed counseling teens about use of tobacco or e-cigarettes can reduce the likelihood that they will start using them, providers were much less likely to discuss e-cigarettes than tobacco with teens.

Nearly all the doctors (97%) reported asking teens about their use of tobacco, but only about half (52%) asked about e-cigarette use (P less than .001). And only about one in five doctors (21%) reported counseling teens about using e-cigarettes, compared with 47% of those who advised teens regarding tobacco use (P = .002).

Over a third of responding physicians (37%) reported helping adolescent patients quit using tobacco, but just 7% reported doing so with e-cigarettes (P less than .001).

Doctors overwhelmingly reported feeling comfortable talking about tobacco with teens (98%), but fewer felt comfortable discussing e-cigarettes (77%; P less than .001). Respondents similarly were less comfortable discussing e-cigarettes (55%) than tobacco (87%) with parents (P less than .001).

Very few pediatricians asked parents about their use of e-cigarettes (5%) or advised them about e-cigarettes’ harms (7%), and even fewer reported helping parents quit using them (2%). By contrast, more than half of pediatricians (60%) asked parents about smoking or advised them about tobacco use harms (52%), and nearly one-third (31%) reported helping parents quit smoking (P less than .001 for all comparisons).

The biggest barrier to discussing e-cigarettes with families was, as with discussing tobacco, not having enough time. But about twice as many respondents cited insufficient knowledge as a barrier for e-cigarettes as for tobacco (P = .003). A small percentage of respondents (less than 20%) also reported feeling unsure about the harm of e-cigarettes (P = .001).

Lack of training was a significant barrier to physicians’ discussion of e-cigarettes as well. Many more physicians reported receiving training in medical school on tobacco and traditional cigarettes (78%) than on e-cigarettes (13%), possibly because of how recently e-cigarettes have become widely available (P less than .001).

More physicians reported receiving training related to e-cigarettes during residency (36%), but it still fell well short of how many reported other tobacco and smoking training during residency (61%; P = .001).

The findings “emphasize the importance of increasing training about e-cig counseling,” Dr. Heinly and her associates concluded.

The researchers noted no external funding or disclosures.

BALTIMORE – Pediatricians appear less comfortable discussing e-cigarettes and their harms with adolescents and parents than they do discussing dangers of tobacco products, according to a recent study.

LiudmylaSupynska/Thinkstock

“Providers are aware of the increased prevalence, harms [of e-cigs] and [the] positive impact of counseling teens about e-cigs,” said Allison Heinly, MD, of Hasbro Children’s Hospital in Providence, R.I., and her colleagues. But, “providers are less likely to ask, advise, or assist parents [and teens] regarding e-cig use, compared to tobacco, and are less comfortable doing so.” The researchers presented their findings at the Pediatric Academic Societies annual meeting.

A variety of concerns exist regarding ingredients in e-cigarettes, Dr. Heinly noted, including nicotine, volatile organic compounds, carcinogenic chemicals, flavorings, and ultra-fine particles.

Dr. Heinly and her associates aimed to assess pediatricians’ knowledge, attitudes, and behaviors toward both teens’ and parents’ use of e-cigarettes, as well as the barrier pediatricians perceived when it came to screening and counseling those who use e-cigarettes.

Among 69 providers at a large Northeastern urban academic primary care clinic who received surveys, 62 responded, primarily residents (84%). The respondents included 44 pediatric residents, eight triple-board residents, and 10 attending physicians.

The researchers collapsed “most of the time”/“always” and “some of the time”/“never” responses into two categories.

Most of the respondents (82%) knew e-cigarettes are the most common tobacco product that youth use, and nearly all (97%) believed e-cigarettes were addictive and harmful to users’ health. In addition, most (79%) believed using e-cigarettes could be a pathway toward students beginning to use other drugs.

Even though respondents believed counseling teens about use of tobacco or e-cigarettes can reduce the likelihood that they will start using them, providers were much less likely to discuss e-cigarettes than tobacco with teens.

Nearly all the doctors (97%) reported asking teens about their use of tobacco, but only about half (52%) asked about e-cigarette use (P less than .001). And only about one in five doctors (21%) reported counseling teens about using e-cigarettes, compared with 47% of those who advised teens regarding tobacco use (P = .002).

Over a third of responding physicians (37%) reported helping adolescent patients quit using tobacco, but just 7% reported doing so with e-cigarettes (P less than .001).

Doctors overwhelmingly reported feeling comfortable talking about tobacco with teens (98%), but fewer felt comfortable discussing e-cigarettes (77%; P less than .001). Respondents similarly were less comfortable discussing e-cigarettes (55%) than tobacco (87%) with parents (P less than .001).

Very few pediatricians asked parents about their use of e-cigarettes (5%) or advised them about e-cigarettes’ harms (7%), and even fewer reported helping parents quit using them (2%). By contrast, more than half of pediatricians (60%) asked parents about smoking or advised them about tobacco use harms (52%), and nearly one-third (31%) reported helping parents quit smoking (P less than .001 for all comparisons).

The biggest barrier to discussing e-cigarettes with families was, as with discussing tobacco, not having enough time. But about twice as many respondents cited insufficient knowledge as a barrier for e-cigarettes as for tobacco (P = .003). A small percentage of respondents (less than 20%) also reported feeling unsure about the harm of e-cigarettes (P = .001).

Lack of training was a significant barrier to physicians’ discussion of e-cigarettes as well. Many more physicians reported receiving training in medical school on tobacco and traditional cigarettes (78%) than on e-cigarettes (13%), possibly because of how recently e-cigarettes have become widely available (P less than .001).

More physicians reported receiving training related to e-cigarettes during residency (36%), but it still fell well short of how many reported other tobacco and smoking training during residency (61%; P = .001).

The findings “emphasize the importance of increasing training about e-cig counseling,” Dr. Heinly and her associates concluded.

The researchers noted no external funding or disclosures.

The Food and Drug Administration has approved a new indication for Zerbaxa (ceftolozane and tazobactam), authorizing it for the treatment of both hospital-acquired and ventilator-associated bacterial pneumonia.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The new indication is for patients 18 years and older. It was based on results of a multinational, double-blind study that compared Zerbaxa with a different antibacterial drug in 726 patients hospitalized with hospital-acquired/ventilator-associated bacterial pneumonia. Mortality and cure rates were similar in the Zerbaxa and comparator groups.

The most common adverse events observed in the trial were elevated liver enzyme levels, renal impairment or failure, and diarrhea. Patients with hypersensitivity to beta-lactam drugs should not be receive Zerbaxa.

“A key global challenge we face as a public health agency is addressing the threat of antimicrobial-resistant infections. Hospital-acquired and ventilator-associated bacterial pneumonia are serious infections that can result in death in some patients. ... That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections,” said Amy Abernethy, MD, PhD, the FDA’s principal deputy commissioner.

Zerbaxa was initially approved in 2014 for treatment of complicated intra-abdominal and urinary tract infections.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved a new indication for Zerbaxa (ceftolozane and tazobactam), authorizing it for the treatment of both hospital-acquired and ventilator-associated bacterial pneumonia.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The new indication is for patients 18 years and older. It was based on results of a multinational, double-blind study that compared Zerbaxa with a different antibacterial drug in 726 patients hospitalized with hospital-acquired/ventilator-associated bacterial pneumonia. Mortality and cure rates were similar in the Zerbaxa and comparator groups.

The most common adverse events observed in the trial were elevated liver enzyme levels, renal impairment or failure, and diarrhea. Patients with hypersensitivity to beta-lactam drugs should not be receive Zerbaxa.

“A key global challenge we face as a public health agency is addressing the threat of antimicrobial-resistant infections. Hospital-acquired and ventilator-associated bacterial pneumonia are serious infections that can result in death in some patients. ... That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections,” said Amy Abernethy, MD, PhD, the FDA’s principal deputy commissioner.

Zerbaxa was initially approved in 2014 for treatment of complicated intra-abdominal and urinary tract infections.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved a new indication for Zerbaxa (ceftolozane and tazobactam), authorizing it for the treatment of both hospital-acquired and ventilator-associated bacterial pneumonia.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The new indication is for patients 18 years and older. It was based on results of a multinational, double-blind study that compared Zerbaxa with a different antibacterial drug in 726 patients hospitalized with hospital-acquired/ventilator-associated bacterial pneumonia. Mortality and cure rates were similar in the Zerbaxa and comparator groups.

The most common adverse events observed in the trial were elevated liver enzyme levels, renal impairment or failure, and diarrhea. Patients with hypersensitivity to beta-lactam drugs should not be receive Zerbaxa.

“A key global challenge we face as a public health agency is addressing the threat of antimicrobial-resistant infections. Hospital-acquired and ventilator-associated bacterial pneumonia are serious infections that can result in death in some patients. ... That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections,” said Amy Abernethy, MD, PhD, the FDA’s principal deputy commissioner.

Zerbaxa was initially approved in 2014 for treatment of complicated intra-abdominal and urinary tract infections.

Find the full press release on the FDA website.

[email protected]

Sequential therapy of oral propranolol then topical timolol for infantile hemangioma helped shorten duration of propranolol and maintain treatment success, according to a study published in Pediatric Dermatology.

hypotekyfidler/Getty Images

Diana B. Mannschreck, BSN, of Johns Hopkins University, Baltimore, and colleagues performed a retrospective chart review of 559 patients with infantile hemangioma seen in the dermatology clinic at Johns Hopkins between December 2008 and January 2018. Patients received any of five courses of treatment, including oral propranolol followed by topical timolol, propranolol only, and timolol only. Of the courses evaluated, propranolol followed by timolol had the shortest duration of propranolol therapy – a median of 2.2 months shorter than propranolol-only therapy (P = .0006). This sequential regimen also was associated with no reinitiations of propranolol therapy following tapering, whereas 13% of those receiving propranolol alone had to reinitiate it after tapering.

This is of interest because oral beta-blockers, including propranolol, have been associated with rare but serious adverse events, such as bronchospasm, hypotension, and hypoglycemia.

Limitations of the study include its retrospective and single-center nature. There was no funding or disclosure information given.

[email protected]

SOURCE: Mannschreck DB et al. Pediatr Dermatol. 2019 Apr 9. doi: 10.1111/pde.13816.

Sequential therapy of oral propranolol then topical timolol for infantile hemangioma helped shorten duration of propranolol and maintain treatment success, according to a study published in Pediatric Dermatology.

hypotekyfidler/Getty Images

Diana B. Mannschreck, BSN, of Johns Hopkins University, Baltimore, and colleagues performed a retrospective chart review of 559 patients with infantile hemangioma seen in the dermatology clinic at Johns Hopkins between December 2008 and January 2018. Patients received any of five courses of treatment, including oral propranolol followed by topical timolol, propranolol only, and timolol only. Of the courses evaluated, propranolol followed by timolol had the shortest duration of propranolol therapy – a median of 2.2 months shorter than propranolol-only therapy (P = .0006). This sequential regimen also was associated with no reinitiations of propranolol therapy following tapering, whereas 13% of those receiving propranolol alone had to reinitiate it after tapering.

This is of interest because oral beta-blockers, including propranolol, have been associated with rare but serious adverse events, such as bronchospasm, hypotension, and hypoglycemia.

Limitations of the study include its retrospective and single-center nature. There was no funding or disclosure information given.

[email protected]

SOURCE: Mannschreck DB et al. Pediatr Dermatol. 2019 Apr 9. doi: 10.1111/pde.13816.

Sequential therapy of oral propranolol then topical timolol for infantile hemangioma helped shorten duration of propranolol and maintain treatment success, according to a study published in Pediatric Dermatology.

hypotekyfidler/Getty Images

Diana B. Mannschreck, BSN, of Johns Hopkins University, Baltimore, and colleagues performed a retrospective chart review of 559 patients with infantile hemangioma seen in the dermatology clinic at Johns Hopkins between December 2008 and January 2018. Patients received any of five courses of treatment, including oral propranolol followed by topical timolol, propranolol only, and timolol only. Of the courses evaluated, propranolol followed by timolol had the shortest duration of propranolol therapy – a median of 2.2 months shorter than propranolol-only therapy (P = .0006). This sequential regimen also was associated with no reinitiations of propranolol therapy following tapering, whereas 13% of those receiving propranolol alone had to reinitiate it after tapering.

This is of interest because oral beta-blockers, including propranolol, have been associated with rare but serious adverse events, such as bronchospasm, hypotension, and hypoglycemia.

Limitations of the study include its retrospective and single-center nature. There was no funding or disclosure information given.

[email protected]

SOURCE: Mannschreck DB et al. Pediatr Dermatol. 2019 Apr 9. doi: 10.1111/pde.13816.

In women with hormone receptor–positive, axillary node–negative breast cancer with Oncotype DX recurrence scores of less than 26, there is minimal to no benefit from chemotherapy, particularly for those greater than age 50 years, according to a clinical practice guideline update by the American Society of Clinical Oncology.

Furthermore, endocrine therapy alone may be offered for patients greater than age 50 years whose tumors have recurrence scores of less than 26, wrote Fabrice Andre, MD, PhD, of Paris Sud University and associates on the expert panel in the Journal of Clinical Oncology.

The panel members reviewed recently published findings from the Trial Assigning Individualized Options for Treatment (TAILORx), which evaluated the clinical utility of the Oncotype DX assay in women with early-stage invasive breast cancer.

“This focused update reviews and analyzes new data regarding these recommendations while applying the same criteria of clinical utility as described in the 2016 guideline,” they wrote.

The expert panel provided recommendations on how to integrate the results of the TAILORx study into clinical practice.

“For patients age 50 years or younger with Oncotype DX recurrence scores of 16-25, clinicians may offer chemoendocrine therapy” the panel wrote. “Patients with Oncotype DX recurrence scores of greater than 30 should be considered candidates for chemoendocrine therapy.”

In addition, on the basis of consensus they recommended that chemoendocrine therapy could be offered to patients with recurrence scores of 26-30.

The panel acknowledged that relevant literature on the use of Oncotype DX in this population will be reviewed over the upcoming months to address anticipated practice deviation related to biomarker testing.

More information on the guidelines is available on the ASCO website.

The study was funded by ASCO. The authors reported financial affiliations with AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Roche, and several others.

SOURCE: Andre F et al. J Clin Oncol. 2019 May 31. doi: 10.1200/JCO.19.00945.

In women with hormone receptor–positive, axillary node–negative breast cancer with Oncotype DX recurrence scores of less than 26, there is minimal to no benefit from chemotherapy, particularly for those greater than age 50 years, according to a clinical practice guideline update by the American Society of Clinical Oncology.

Furthermore, endocrine therapy alone may be offered for patients greater than age 50 years whose tumors have recurrence scores of less than 26, wrote Fabrice Andre, MD, PhD, of Paris Sud University and associates on the expert panel in the Journal of Clinical Oncology.

The panel members reviewed recently published findings from the Trial Assigning Individualized Options for Treatment (TAILORx), which evaluated the clinical utility of the Oncotype DX assay in women with early-stage invasive breast cancer.

“This focused update reviews and analyzes new data regarding these recommendations while applying the same criteria of clinical utility as described in the 2016 guideline,” they wrote.

The expert panel provided recommendations on how to integrate the results of the TAILORx study into clinical practice.

“For patients age 50 years or younger with Oncotype DX recurrence scores of 16-25, clinicians may offer chemoendocrine therapy” the panel wrote. “Patients with Oncotype DX recurrence scores of greater than 30 should be considered candidates for chemoendocrine therapy.”

In addition, on the basis of consensus they recommended that chemoendocrine therapy could be offered to patients with recurrence scores of 26-30.

The panel acknowledged that relevant literature on the use of Oncotype DX in this population will be reviewed over the upcoming months to address anticipated practice deviation related to biomarker testing.

More information on the guidelines is available on the ASCO website.

The study was funded by ASCO. The authors reported financial affiliations with AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Roche, and several others.

SOURCE: Andre F et al. J Clin Oncol. 2019 May 31. doi: 10.1200/JCO.19.00945.

In women with hormone receptor–positive, axillary node–negative breast cancer with Oncotype DX recurrence scores of less than 26, there is minimal to no benefit from chemotherapy, particularly for those greater than age 50 years, according to a clinical practice guideline update by the American Society of Clinical Oncology.

Furthermore, endocrine therapy alone may be offered for patients greater than age 50 years whose tumors have recurrence scores of less than 26, wrote Fabrice Andre, MD, PhD, of Paris Sud University and associates on the expert panel in the Journal of Clinical Oncology.

The panel members reviewed recently published findings from the Trial Assigning Individualized Options for Treatment (TAILORx), which evaluated the clinical utility of the Oncotype DX assay in women with early-stage invasive breast cancer.

“This focused update reviews and analyzes new data regarding these recommendations while applying the same criteria of clinical utility as described in the 2016 guideline,” they wrote.

The expert panel provided recommendations on how to integrate the results of the TAILORx study into clinical practice.

“For patients age 50 years or younger with Oncotype DX recurrence scores of 16-25, clinicians may offer chemoendocrine therapy” the panel wrote. “Patients with Oncotype DX recurrence scores of greater than 30 should be considered candidates for chemoendocrine therapy.”

In addition, on the basis of consensus they recommended that chemoendocrine therapy could be offered to patients with recurrence scores of 26-30.

The panel acknowledged that relevant literature on the use of Oncotype DX in this population will be reviewed over the upcoming months to address anticipated practice deviation related to biomarker testing.

More information on the guidelines is available on the ASCO website.

The study was funded by ASCO. The authors reported financial affiliations with AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Roche, and several others.

SOURCE: Andre F et al. J Clin Oncol. 2019 May 31. doi: 10.1200/JCO.19.00945.

The Food and Drug Administration has announced the clearance of a modified multipatient-use endoscope connector, which was designed to reduce the risk of cross-contamination previously identified by the FDA.

Wikimedia Commons/FitzColinGerald/Creative Commons License

AGA Center for GI Innovation and Technology  will continue to monitor this issue and encourages all GIs to follow the most up-to-date FDA guidance.

[email protected]

The Food and Drug Administration has announced the clearance of a modified multipatient-use endoscope connector, which was designed to reduce the risk of cross-contamination previously identified by the FDA.

Wikimedia Commons/FitzColinGerald/Creative Commons License

AGA Center for GI Innovation and Technology  will continue to monitor this issue and encourages all GIs to follow the most up-to-date FDA guidance.

[email protected]

The Food and Drug Administration has announced the clearance of a modified multipatient-use endoscope connector, which was designed to reduce the risk of cross-contamination previously identified by the FDA.

Wikimedia Commons/FitzColinGerald/Creative Commons License

AGA Center for GI Innovation and Technology  will continue to monitor this issue and encourages all GIs to follow the most up-to-date FDA guidance.

[email protected]

Excessive postpartum bleeding is a major cause of maternal morbidity and mortality. Worldwide, obstetric hemorrhage is the most common cause of maternal death.^1,2 Medications reported to reduce postpartum bleeding include oxytocin, misoprostol, ergonovine, methylergonovine, carboprost, and tranexamic acid. A recent Cochrane network meta-analysis of 196 trials, including 135,559 women, distilled in 1,361 pages of analysis, reported on the medications associated with the greatest reduction in postpartum bleeding.³ Surprisingly, for preventing blood loss ≥ 500 mL, misoprostol plus oxytocin and ergonovine plus oxytocin were the highest ranked interventions. This evidence is summarized here.

Misoprostol plus oxytocin

After newborn delivery, active management of the third stage of labor, including uterotonic administration, is strongly recommended because it will reduce postpartum blood loss, decreasing the rate of postpartum hemorrhage (PPH).⁴ Both oxytocin and misoprostol are effective uterotonics. However, the combination of oxytocin plus misoprostol appears to be more effective than oxytocin alone in reducing the frequency of postpartum blood loss greater than 500 mL.³ To understand the clinical efficacy and adverse effects (AEs) of combined oxytocin plus misoprostol a meta-analysis was performed for both vaginal and cesarean deliveries (CDs).

Efficacy and AEs during vaginal delivery. In the meta-analysis, about 6,000 vaginal deliveries were analyzed, with no significant differences for misoprostol plus oxytocin versus oxytocin alone found for the following outcomes: maternal death, intensive care unit admissions, and rate of blood loss ≥ 1,000 mL (1.7% for both uterotonics vs 2.2% for oxytocin alone).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (0.95% vs 2.5%), reduced risk of blood loss ≥ 500 mL (5.9% vs 8.0%), reduced risk of requiring an additional uterotonic (3.6% vs 5.8%), and a smaller decrease in hemoglobin concentration from pre- to postdelivery (-0.89 g/L).³

In my opinion, the difference in hemoglobin concentration, although statistically significant, is not of clinical significance. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (2.4% vs 0.66%), vomiting (3.1% vs 0.86%), and fever (21% vs 3.9%).³ A weakness of this meta-analysis is that the trials used a wide range of misoprostol dosages (200 to 600 µg) and multiple routes of administration, including sublingual (under the tongue), buccal, and rectal. This makes it impossible to identify a best misoprostol dosage and administration route.

Efficacy and AEs during CD. In the same meta-analysis about 2,000 CDs were analyzed, with no significant difference for misoprostol plus oxytocin versus oxytocin alone for the following outcomes: maternal death, intensive care unit admissions, and PPH ≥ 1,000 mL blood loss (6.2% vs 6.5%).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (2.6% vs 5.4%), reduced risk of blood loss ≥ 500 mL (32% vs 47%), reduced risk of requiring an additional uterotonic (14% vs 28%), and a smaller decrease in hemoglobin concentration from before to after delivery (-4.0 g/L).³ In my opinion, the statistically significant difference in hemoglobin concentration is not clinically significant. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (12% vs 6.1%), vomiting (8.1% vs 5.4%), shivering (13% vs 7%), and fever (7.7% vs 4.0%).³

Continue to: Ergonovine plus oxytocin...

Ergonovine plus oxytocin

Ergonovine is an ergot derivative that causes uterine contractions and has been shown to effectively reduce blood loss at delivery. In the United States a methyl-derivative of ergonovine, methylergonovine, is widely available. In a meta-analysis with mostly vaginal deliveries, there were no significant differences for ergonovine plus oxytocin versus oxytocin alone for the following outcomes: death, intensive care unit admission, rate of blood loss ≥ 1,000 mL(2.0% vs 2.7%), blood transfusion, administration of an additional uterotonic, change in hemoglobin from pre- to postdelivery, nausea, hypertension, shivering, and fever.³ However, ergonovine plus oxytocin, compared with oxytocin alone, resulted in a significantly reduced rate of blood loss ≥ 500 mL (8.3% vs 10.2%) and an increased rate of vomiting (8.1% vs 1.6%).³ In these trials women with a blood pressure ≥ 150/100 mm Hg were generally excluded from receiving ergonovine because of its hypertensive effect.

Clinical practice options

Given the Cochrane meta-analysis results, ObGyns have two approaches for optimizing PPH reduction.

Option 1: Use a single uterotonic to reduce postpartum blood loss. If excess bleeding occurs, rapidly administer a second uterotonic agent. Currently, monotherapy with intravenous or intramuscular oxytocin is the standard for reducing postpartum blood loss.^5,6 Advantages of this approach compared with dual agent therapy include simplification of care and minimization of AEs. However, oxytocin monotherapy for minimizing postpartum bleeding may be suboptimal. In the largest trial ever performed (involving 29,645 women) when oxytocin was administered postpartum, the rates of estimated blood loss ≥ 500 mL and ≥ 1,000 mL were 9.1% and 1.45%, respectively.⁵ Is 9% an optimal rate for blood loss ≥ 500 mL following a vaginal delivery? Or should we try to achieve a lower rate?

Given the “high” rate of blood loss ≥ 500 mL with oxytocin alone, it is important for clinicians using the one-uterotonic approach to promptly recognize patients who have excessive bleeding and transition rapidly from prevention to treatment. When PPH cases are reviewed, a common finding is that the clinicians did not timely recognize excess bleeding, delaying transition to treatment with additional uterotonics and other interventions. When routinely using oxytocin monotherapy, lowering the threshold for administering a second uterotonic (methylergonovine, carboprost, misoprostol, or tranexamic acid) may help decrease the frequency of excess postpartum blood loss.

Option 2: Administer two uterotonics to reduce postpartum blood loss at all deliveries. Given the “high” rate of excess postpartum blood loss with oxytocin monotherapy, an alternative is to administer two uterotonics at all births or at births with a high risk of excess blood loss. As discussed, administering two uterotonics, oxytocin plus misoprostol or oxytocin plus ergonovine, has been reported to be more effective than oxytocin alone for reducing postpartum bleeding ≥ 500 mL.³ In the Cochrane meta-analysis, per 1,000 women given oxytocin following a vaginal birth, 122 would have blood loss ≥ 500 mL, compared with 85 given oxytocin plus misoprostol or oxytocin plus ergonovine.³

Misoprostol is administered sublingually, buccally, or rectally, and methylergonovine is administered by intramuscular injection. Although dual uterotonic therapy is more effective than monotherapy, dual therapy is associated with more AEs. As noted, compared with oxytocin monotherapy, the combination of oxytocin plus misoprostol is associated with more nausea, vomiting, shivering, and fever. Oxytocin plus ergonovine is associated with a higher rate of vomiting than oxytocin monotherapy. In my practice I prefer using intramuscular methylergonovine as the second agent to avoid the high rate of fever associated with misoprostol.

For dual agent therapy, one approach is to administer misoprostol 200 µg or 400 µg through the buccal^7,8 or sublingual^9,10 routes. Higher dosages of misoprostol (600 µg to 800 µg) have been used^11,12 but are likely associated with higher rates of nausea, vomiting,shivering, and fever than the lower dosages. Methylergonovine 0.2 mg is administered intramuscularly.

Continue to: The bottom line...

The bottom line

PPH is a major cause of maternal morbidity, and in low-resource settings, mortality. Oxytocin is the standard for reducing postpartum blood loss, but rates of blood loss ≥ 500 mL are high following this monotherapy. To reduce postpartum blood loss beyond what is possible with oxytocin alone, clinicians can more rapidly transition to administering a second uterotonic when they suspect blood loss is becoming excessive or they can use two uterotonic agents with all births or in those at high risk for excess bleeding. If blood loss does become excessive, clinicians need to pivot rapidly from prevention with oxytocin to treatment with our entire therapeutic armamentarium.

Excessive postpartum bleeding is a major cause of maternal morbidity and mortality. Worldwide, obstetric hemorrhage is the most common cause of maternal death.^1,2 Medications reported to reduce postpartum bleeding include oxytocin, misoprostol, ergonovine, methylergonovine, carboprost, and tranexamic acid. A recent Cochrane network meta-analysis of 196 trials, including 135,559 women, distilled in 1,361 pages of analysis, reported on the medications associated with the greatest reduction in postpartum bleeding.³ Surprisingly, for preventing blood loss ≥ 500 mL, misoprostol plus oxytocin and ergonovine plus oxytocin were the highest ranked interventions. This evidence is summarized here.

Misoprostol plus oxytocin

After newborn delivery, active management of the third stage of labor, including uterotonic administration, is strongly recommended because it will reduce postpartum blood loss, decreasing the rate of postpartum hemorrhage (PPH).⁴ Both oxytocin and misoprostol are effective uterotonics. However, the combination of oxytocin plus misoprostol appears to be more effective than oxytocin alone in reducing the frequency of postpartum blood loss greater than 500 mL.³ To understand the clinical efficacy and adverse effects (AEs) of combined oxytocin plus misoprostol a meta-analysis was performed for both vaginal and cesarean deliveries (CDs).

Efficacy and AEs during vaginal delivery. In the meta-analysis, about 6,000 vaginal deliveries were analyzed, with no significant differences for misoprostol plus oxytocin versus oxytocin alone found for the following outcomes: maternal death, intensive care unit admissions, and rate of blood loss ≥ 1,000 mL (1.7% for both uterotonics vs 2.2% for oxytocin alone).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (0.95% vs 2.5%), reduced risk of blood loss ≥ 500 mL (5.9% vs 8.0%), reduced risk of requiring an additional uterotonic (3.6% vs 5.8%), and a smaller decrease in hemoglobin concentration from pre- to postdelivery (-0.89 g/L).³

In my opinion, the difference in hemoglobin concentration, although statistically significant, is not of clinical significance. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (2.4% vs 0.66%), vomiting (3.1% vs 0.86%), and fever (21% vs 3.9%).³ A weakness of this meta-analysis is that the trials used a wide range of misoprostol dosages (200 to 600 µg) and multiple routes of administration, including sublingual (under the tongue), buccal, and rectal. This makes it impossible to identify a best misoprostol dosage and administration route.

Efficacy and AEs during CD. In the same meta-analysis about 2,000 CDs were analyzed, with no significant difference for misoprostol plus oxytocin versus oxytocin alone for the following outcomes: maternal death, intensive care unit admissions, and PPH ≥ 1,000 mL blood loss (6.2% vs 6.5%).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (2.6% vs 5.4%), reduced risk of blood loss ≥ 500 mL (32% vs 47%), reduced risk of requiring an additional uterotonic (14% vs 28%), and a smaller decrease in hemoglobin concentration from before to after delivery (-4.0 g/L).³ In my opinion, the statistically significant difference in hemoglobin concentration is not clinically significant. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (12% vs 6.1%), vomiting (8.1% vs 5.4%), shivering (13% vs 7%), and fever (7.7% vs 4.0%).³

Continue to: Ergonovine plus oxytocin...

Ergonovine plus oxytocin

Ergonovine is an ergot derivative that causes uterine contractions and has been shown to effectively reduce blood loss at delivery. In the United States a methyl-derivative of ergonovine, methylergonovine, is widely available. In a meta-analysis with mostly vaginal deliveries, there were no significant differences for ergonovine plus oxytocin versus oxytocin alone for the following outcomes: death, intensive care unit admission, rate of blood loss ≥ 1,000 mL(2.0% vs 2.7%), blood transfusion, administration of an additional uterotonic, change in hemoglobin from pre- to postdelivery, nausea, hypertension, shivering, and fever.³ However, ergonovine plus oxytocin, compared with oxytocin alone, resulted in a significantly reduced rate of blood loss ≥ 500 mL (8.3% vs 10.2%) and an increased rate of vomiting (8.1% vs 1.6%).³ In these trials women with a blood pressure ≥ 150/100 mm Hg were generally excluded from receiving ergonovine because of its hypertensive effect.

Clinical practice options

Given the Cochrane meta-analysis results, ObGyns have two approaches for optimizing PPH reduction.

Option 1: Use a single uterotonic to reduce postpartum blood loss. If excess bleeding occurs, rapidly administer a second uterotonic agent. Currently, monotherapy with intravenous or intramuscular oxytocin is the standard for reducing postpartum blood loss.^5,6 Advantages of this approach compared with dual agent therapy include simplification of care and minimization of AEs. However, oxytocin monotherapy for minimizing postpartum bleeding may be suboptimal. In the largest trial ever performed (involving 29,645 women) when oxytocin was administered postpartum, the rates of estimated blood loss ≥ 500 mL and ≥ 1,000 mL were 9.1% and 1.45%, respectively.⁵ Is 9% an optimal rate for blood loss ≥ 500 mL following a vaginal delivery? Or should we try to achieve a lower rate?

Given the “high” rate of blood loss ≥ 500 mL with oxytocin alone, it is important for clinicians using the one-uterotonic approach to promptly recognize patients who have excessive bleeding and transition rapidly from prevention to treatment. When PPH cases are reviewed, a common finding is that the clinicians did not timely recognize excess bleeding, delaying transition to treatment with additional uterotonics and other interventions. When routinely using oxytocin monotherapy, lowering the threshold for administering a second uterotonic (methylergonovine, carboprost, misoprostol, or tranexamic acid) may help decrease the frequency of excess postpartum blood loss.

Option 2: Administer two uterotonics to reduce postpartum blood loss at all deliveries. Given the “high” rate of excess postpartum blood loss with oxytocin monotherapy, an alternative is to administer two uterotonics at all births or at births with a high risk of excess blood loss. As discussed, administering two uterotonics, oxytocin plus misoprostol or oxytocin plus ergonovine, has been reported to be more effective than oxytocin alone for reducing postpartum bleeding ≥ 500 mL.³ In the Cochrane meta-analysis, per 1,000 women given oxytocin following a vaginal birth, 122 would have blood loss ≥ 500 mL, compared with 85 given oxytocin plus misoprostol or oxytocin plus ergonovine.³

Misoprostol is administered sublingually, buccally, or rectally, and methylergonovine is administered by intramuscular injection. Although dual uterotonic therapy is more effective than monotherapy, dual therapy is associated with more AEs. As noted, compared with oxytocin monotherapy, the combination of oxytocin plus misoprostol is associated with more nausea, vomiting, shivering, and fever. Oxytocin plus ergonovine is associated with a higher rate of vomiting than oxytocin monotherapy. In my practice I prefer using intramuscular methylergonovine as the second agent to avoid the high rate of fever associated with misoprostol.

For dual agent therapy, one approach is to administer misoprostol 200 µg or 400 µg through the buccal^7,8 or sublingual^9,10 routes. Higher dosages of misoprostol (600 µg to 800 µg) have been used^11,12 but are likely associated with higher rates of nausea, vomiting,shivering, and fever than the lower dosages. Methylergonovine 0.2 mg is administered intramuscularly.

Continue to: The bottom line...

The bottom line

PPH is a major cause of maternal morbidity, and in low-resource settings, mortality. Oxytocin is the standard for reducing postpartum blood loss, but rates of blood loss ≥ 500 mL are high following this monotherapy. To reduce postpartum blood loss beyond what is possible with oxytocin alone, clinicians can more rapidly transition to administering a second uterotonic when they suspect blood loss is becoming excessive or they can use two uterotonic agents with all births or in those at high risk for excess bleeding. If blood loss does become excessive, clinicians need to pivot rapidly from prevention with oxytocin to treatment with our entire therapeutic armamentarium.

Excessive postpartum bleeding is a major cause of maternal morbidity and mortality. Worldwide, obstetric hemorrhage is the most common cause of maternal death.^1,2 Medications reported to reduce postpartum bleeding include oxytocin, misoprostol, ergonovine, methylergonovine, carboprost, and tranexamic acid. A recent Cochrane network meta-analysis of 196 trials, including 135,559 women, distilled in 1,361 pages of analysis, reported on the medications associated with the greatest reduction in postpartum bleeding.³ Surprisingly, for preventing blood loss ≥ 500 mL, misoprostol plus oxytocin and ergonovine plus oxytocin were the highest ranked interventions. This evidence is summarized here.

Misoprostol plus oxytocin

After newborn delivery, active management of the third stage of labor, including uterotonic administration, is strongly recommended because it will reduce postpartum blood loss, decreasing the rate of postpartum hemorrhage (PPH).⁴ Both oxytocin and misoprostol are effective uterotonics. However, the combination of oxytocin plus misoprostol appears to be more effective than oxytocin alone in reducing the frequency of postpartum blood loss greater than 500 mL.³ To understand the clinical efficacy and adverse effects (AEs) of combined oxytocin plus misoprostol a meta-analysis was performed for both vaginal and cesarean deliveries (CDs).

Efficacy and AEs during vaginal delivery. In the meta-analysis, about 6,000 vaginal deliveries were analyzed, with no significant differences for misoprostol plus oxytocin versus oxytocin alone found for the following outcomes: maternal death, intensive care unit admissions, and rate of blood loss ≥ 1,000 mL (1.7% for both uterotonics vs 2.2% for oxytocin alone).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (0.95% vs 2.5%), reduced risk of blood loss ≥ 500 mL (5.9% vs 8.0%), reduced risk of requiring an additional uterotonic (3.6% vs 5.8%), and a smaller decrease in hemoglobin concentration from pre- to postdelivery (-0.89 g/L).³

In my opinion, the difference in hemoglobin concentration, although statistically significant, is not of clinical significance. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (2.4% vs 0.66%), vomiting (3.1% vs 0.86%), and fever (21% vs 3.9%).³ A weakness of this meta-analysis is that the trials used a wide range of misoprostol dosages (200 to 600 µg) and multiple routes of administration, including sublingual (under the tongue), buccal, and rectal. This makes it impossible to identify a best misoprostol dosage and administration route.

Efficacy and AEs during CD. In the same meta-analysis about 2,000 CDs were analyzed, with no significant difference for misoprostol plus oxytocin versus oxytocin alone for the following outcomes: maternal death, intensive care unit admissions, and PPH ≥ 1,000 mL blood loss (6.2% vs 6.5%).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (2.6% vs 5.4%), reduced risk of blood loss ≥ 500 mL (32% vs 47%), reduced risk of requiring an additional uterotonic (14% vs 28%), and a smaller decrease in hemoglobin concentration from before to after delivery (-4.0 g/L).³ In my opinion, the statistically significant difference in hemoglobin concentration is not clinically significant. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (12% vs 6.1%), vomiting (8.1% vs 5.4%), shivering (13% vs 7%), and fever (7.7% vs 4.0%).³

Continue to: Ergonovine plus oxytocin...

Ergonovine plus oxytocin

Ergonovine is an ergot derivative that causes uterine contractions and has been shown to effectively reduce blood loss at delivery. In the United States a methyl-derivative of ergonovine, methylergonovine, is widely available. In a meta-analysis with mostly vaginal deliveries, there were no significant differences for ergonovine plus oxytocin versus oxytocin alone for the following outcomes: death, intensive care unit admission, rate of blood loss ≥ 1,000 mL(2.0% vs 2.7%), blood transfusion, administration of an additional uterotonic, change in hemoglobin from pre- to postdelivery, nausea, hypertension, shivering, and fever.³ However, ergonovine plus oxytocin, compared with oxytocin alone, resulted in a significantly reduced rate of blood loss ≥ 500 mL (8.3% vs 10.2%) and an increased rate of vomiting (8.1% vs 1.6%).³ In these trials women with a blood pressure ≥ 150/100 mm Hg were generally excluded from receiving ergonovine because of its hypertensive effect.

Clinical practice options

Given the Cochrane meta-analysis results, ObGyns have two approaches for optimizing PPH reduction.

Option 1: Use a single uterotonic to reduce postpartum blood loss. If excess bleeding occurs, rapidly administer a second uterotonic agent. Currently, monotherapy with intravenous or intramuscular oxytocin is the standard for reducing postpartum blood loss.^5,6 Advantages of this approach compared with dual agent therapy include simplification of care and minimization of AEs. However, oxytocin monotherapy for minimizing postpartum bleeding may be suboptimal. In the largest trial ever performed (involving 29,645 women) when oxytocin was administered postpartum, the rates of estimated blood loss ≥ 500 mL and ≥ 1,000 mL were 9.1% and 1.45%, respectively.⁵ Is 9% an optimal rate for blood loss ≥ 500 mL following a vaginal delivery? Or should we try to achieve a lower rate?

Given the “high” rate of blood loss ≥ 500 mL with oxytocin alone, it is important for clinicians using the one-uterotonic approach to promptly recognize patients who have excessive bleeding and transition rapidly from prevention to treatment. When PPH cases are reviewed, a common finding is that the clinicians did not timely recognize excess bleeding, delaying transition to treatment with additional uterotonics and other interventions. When routinely using oxytocin monotherapy, lowering the threshold for administering a second uterotonic (methylergonovine, carboprost, misoprostol, or tranexamic acid) may help decrease the frequency of excess postpartum blood loss.

Option 2: Administer two uterotonics to reduce postpartum blood loss at all deliveries. Given the “high” rate of excess postpartum blood loss with oxytocin monotherapy, an alternative is to administer two uterotonics at all births or at births with a high risk of excess blood loss. As discussed, administering two uterotonics, oxytocin plus misoprostol or oxytocin plus ergonovine, has been reported to be more effective than oxytocin alone for reducing postpartum bleeding ≥ 500 mL.³ In the Cochrane meta-analysis, per 1,000 women given oxytocin following a vaginal birth, 122 would have blood loss ≥ 500 mL, compared with 85 given oxytocin plus misoprostol or oxytocin plus ergonovine.³

Misoprostol is administered sublingually, buccally, or rectally, and methylergonovine is administered by intramuscular injection. Although dual uterotonic therapy is more effective than monotherapy, dual therapy is associated with more AEs. As noted, compared with oxytocin monotherapy, the combination of oxytocin plus misoprostol is associated with more nausea, vomiting, shivering, and fever. Oxytocin plus ergonovine is associated with a higher rate of vomiting than oxytocin monotherapy. In my practice I prefer using intramuscular methylergonovine as the second agent to avoid the high rate of fever associated with misoprostol.

For dual agent therapy, one approach is to administer misoprostol 200 µg or 400 µg through the buccal^7,8 or sublingual^9,10 routes. Higher dosages of misoprostol (600 µg to 800 µg) have been used^11,12 but are likely associated with higher rates of nausea, vomiting,shivering, and fever than the lower dosages. Methylergonovine 0.2 mg is administered intramuscularly.

Continue to: The bottom line...

The bottom line

PPH is a major cause of maternal morbidity, and in low-resource settings, mortality. Oxytocin is the standard for reducing postpartum blood loss, but rates of blood loss ≥ 500 mL are high following this monotherapy. To reduce postpartum blood loss beyond what is possible with oxytocin alone, clinicians can more rapidly transition to administering a second uterotonic when they suspect blood loss is becoming excessive or they can use two uterotonic agents with all births or in those at high risk for excess bleeding. If blood loss does become excessive, clinicians need to pivot rapidly from prevention with oxytocin to treatment with our entire therapeutic armamentarium.